Feline primary somatosensory cortical neurons were studied with compound multibarrell micropipettes using the technique of combined penicillin and amino acid iontophoresis. Units had inhibitory responses to GABA, ALA and GLY and excitatory responses to HC and GLU. Topical penicillin, strychnine or bicuculline failed to consistently antagonize amino acid responses of units at cortical depths of 1-2mm. Penicillin iontophoresis (100-500nA) resulted in reversible nonspecific antagonism of all three inhibitory agents in order of potency GLY greater than ALA greater than GABA. Penicillin iontophoresis in higher dosage resulted in development of a micro epileptic focus in which decreased amino acid responses were observed. Penicillin iontophoresis in lower dosage resulted in enhanced physiological responses which were not correlated with decreased amino acid responses. Amino acid antagonism by penicillin appeared unlikely to be the primary mechanism by which penicillin produced epileptic foci.